Does vitamin D deficiency contribute to erectile dysfunction?

Dermato-Endocrinology 4:2, 128–136; April/May/June 2012; G 2012 Landes Bioscience Does vitamin D deficiency contribute to erectile dysfunction? Marc B. Sorenson1,* and William B. Grant2 1 Sunlight Institute; Saint George, UT USA; 2Sunlight, Nutrition, and Health Research Center; San Francisco, CA USA . e nc Keywords: vitamin D, erectile dysfunction, vascular diseases, peripheral arterial disease, nitric oxide, inflammation, calcification, hypertension, diabetes, vasodilation Abbreviations: CAM, cellular adhesion molecules; 95% CI, 95% confidence interval; CRP, C-reactive protein; CVD, cardiovascular disease; DM, diabetes mellitus; ED, erectile dysfunction; END, endothelial dysfunction; NO, nitric oxide; NOS, nitric oxide synthases; PAD, peripheral arterial disease; UVB, ultraviolet-B; VDD, vitamin D deficiency e i c s o i B . e s t e u d b i n r a t L s i 2 d 1 t 0 o 2 n o © D Erectile dysfunction (ED) is a multifactorial disease, and its causes can be neurogenic, psychogenic, hormonal and vascular. ED is often an important indicator of cardiovascular disease (CVD) and a powerful early marker for asymptomatic CVD. Erection is a vascular event, and ED is often a vascular disease caused by endothelial damage and subsequent inhibition of vasodilation. We show here that risk factors associated with a higher CVD risk also associate with a higher ED risk. Such factors include diabetes mellitus, hypertension, arterial calcification and Inflammation in the vascular endothelium. Vitamin D deficiency is one of several dynamics that associates with increased CVD risk, but to our knowledge, it has not been studied as a possible contributor to ED. Here we examine research linking ED and CVD and discuss how vitamin D influences CVD and its classic risk factors—factors that also associate to increased ED risk. We also summarize research indicating that vitamin D associates with reduced risk of several nonvascular contributing factors for ED. We conclude that VDD contributes to ED. This hypothesis should be tested through observational and intervention studies. Introduction: Important Facts Pertaining to this Discussion Vitamin D is a steroid hormone produced in human skin by sunlight stimulation, specifically the ultraviolet-B (UVB) portion of the sunlight spectrum; about 80% of vitamin D is thus obtained.1 The angle of sunlight varies greatly by season. In summer, the sun is overhead at noon, but in winter it stays closer to the horizon, and sunlight must pass through more atmosphere, which filters out much or all of the UVB. Therefore, availability of UVB exposure, and its resultant vitamin D production in skin, is highest in late spring through early fall and lowest from late fall through early spring. Consequently, vitamin D levels in the bloodstream also vary by season, with levels highest in late spring through early fall and lowest from late fall through early spring. *Correspondence to: Marc B. Sorenson; Email: Submitted: 01/12/12; Revised: 04/04/12; Accepted: 04/11/12 http://dx.doi.org/10.4161/derm.20361 128 For example, vitamin D levels in the UK are about 50% higher at the end of summer than at the end of winter.1 Vitamin D deficiency (VDD) has increased profoundly in the last two decades. According to data from the National Health and Nutrition Examination Survey (NHANES), 45% of the US population had serum vitamin D levels of 30 ng/mL (considered adequate for health2) in 1998–1994, whereas in 2001–2004, this figure was only 23%, a drop of 49%.3 Concomitantly, the incidence of erectile dysfunction (ED) is rising: worldwide, the number of men with ED will increase from 150 million in 1995 to an estimated 322 million in 2025.4 ED is also prevalent in the US, affecting approximately 18–30 million men older than 20 y.5,6 Much of the worldwide upsurge may be due to an aging population, a deteriorating diet, lack of exercise and other unhealthful practices. One recent study found risk of ED associated with “body mass index (BMI), irritative lower urinary tract symptoms, diabetes mellitus, chronic obstructive pulmonary disease (COPD) and sexual inactivity.”7 “Most cases [of ED] have a multifactorial origin and it is admitted the influence on its pathogenesis of systemic diseases, different kind of drugs, psychogenic factors, cardiovascular, endocrinological and neurological diseases. Neurologic causes of erectile dysfunction may have their origins in the central or peripheral nervous system. Among possible process of neurogenic erectile dysfunction of central origin would be tumors, cerebral vascular accidents, encephalitis, Parkinson disease, multiple sclerosis and other demyelinization diseases, dementias, olivopontocerebellar degeneration and epilepsy.”8 It has been estimated that about half of ED is related to vascular causes.9 VDD also contributes to ED apart from its negative influence on classic CVD risk factors. The Role of Vascular Disorders in ED ED is an inability to produce an erection sufficiently rigid for sexual intercourse. ED incidence increases with age; the most severe form (defined as never being able to achieve an erection) occurs in 2% of men aged 20–39 y, increasing to 47% of men aged 75 y.10 Dermato-Endocrinology Volume 4 Issue 2 REVIEW The penis is a highly vascularized organ, and erections are primarily vascular events.11 Sexual stimulation causes the release of neurotransmitters from the corpus cavernosa (the two cylindrical chambers that run the length of the penis) and a relaxing factor, now established as nitric oxide (NO), from the endothelial cells of the penis.12 NO is particularly important; vasodilation is essential to erection, and NO is the trigger for vasodilation in the vascular endothelium.13,14 The neurotransmitters, together with NO, cause the corpus cavernosa to relax and allow blood to flow into the penis, causing the penis to expand and sustain an erection until the process is reversed.15 Any disorder causing endothelial dysfunction (END) will also interfere with vasodilation, which prevents erection. END is an early marker for the development of atherosclerosis.16 In fact, END is the key factor in the pathophysiology of ED, and men with penile END also have END in other blood vessels.17 The increase in the number of patients with CVD risk factors parallels the worldwide increase in ED prevalence,18 which one would expect given that the two disorders result from intertwined disease processes.19 Although nonvascular factors such as depression, fatigue, stress, Parkinson disease, multiple sclerosis (MS), and hypertensive medications may affect ED,12 it is primarily a vasculogenic disease. Its most prevalent cause is the arterial occlusion of atherosclerosis, which also affects the coronary arteries and can lead to heart attack11 or, in other parts of the body, vascular events such as stroke20 and peripheral arterial disease (PAD).21 Because the penile arteries are smaller than arteries supplying other areas of the body, t (...truncated)